- Endothelial NOS
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Endothelial NOS (eNOS), also known as nitric oxide synthase 3 (NOS3) or constitutive NOS (cNOS), is an enzyme that in humans is encoded by the NOS3 gene.[1]
Endothelial NOS is a nitric oxide synthase that generates NO in blood vessels and is involved with regulating vascular tone by inhibiting smooth muscle contraction and platelet aggregation. A constitutive Ca2+ dependent NOS provides a basal release of NO. eNOS is associated with plasma membranes surrounding cells and the membranes of Golgi bodies within cells.
Contents
Clinical significance
Variations in this gene are associated with susceptibility to coronary spasm.[2]
An association between a polymorphism in the gene and late-onset Alzheimer's disease in Chinese have been reported.[3]
Interactions
Endothelial NOS has been shown to interact with CAV1,[4] HSP90AA1[5][6][7] and GUCY1B3.[5]
References
- ^ Marsden PA, Schappert KT, Chen HS, Flowers M, Sundell CL, Wilcox JN, Lamas S, Michel T (August 1992). "Molecular cloning and characterization of human endothelial nitric oxide synthase". FEBS Lett. 307 (3): 287–93. doi:10.1016/0014-5793(92)80697-F. PMID 1379542.
- ^ Yoshimura M, Yasue H, Nakayama M, Shimasaki Y, Sumida H, Sugiyama S, Kugiyama K, Ogawa H, Ogawa Y, Saito Y, Miyamoto Y, Nakao K (July 1998). "A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese". Hum. Genet. 103 (1): 65–9. doi:10.1007/s004390050785. PMID 9737779.
- ^ Wang B, Tan S, Yang Z, Xie YC, Wang J, Zhou S, Li S, Zheng C, Ma X (February 2008). "Association between Alzheimer's disease and the NOS3 gene Glu298Asp polymorphism in Chinese". J. Mol. Neurosci. 34 (2): 173–6. doi:10.1007/s12031-007-9026-6. PMID 18183499.
- ^ García-Cardeña G, Fan R, Stern DF, Liu J, Sessa WC (November 1996). "Endothelial nitric oxide synthase is regulated by tyrosine phosphorylation and interacts with caveolin-1". J. Biol. Chem. 271 (44): 27237–40. doi:10.1074/jbc.271.44.27237. PMID 8910295.
- ^ a b Venema RC, Venema VJ, Ju H, Harris MB, Snead C, Jilling T, Dimitropoulou C, Maragoudakis ME, Catravas JD (August 2003). "Novel complexes of guanylate cyclase with heat shock protein 90 and nitric oxide synthase". Am. J. Physiol. Heart Circ. Physiol. 285 (2): H669–78. doi:10.1152/ajpheart.01025.2002. PMID 12676772.
- ^ Harris MB, Ju H, Venema VJ, Blackstone M, Venema RC (September 2000). "Role of heat shock protein 90 in bradykinin-stimulated endothelial nitric oxide release". Gen. Pharmacol. 35 (3): 165–70. doi:10.1016/S0306-3623(01)00104-5. PMID 11744239.
- ^ Stepp DW, Ou J, Ackerman AW, Welak S, Klick D, Pritchard KA (August 2002). "Native LDL and minimally oxidized LDL differentially regulate superoxide anion in vascular endothelium in situ". Am. J. Physiol. Heart Circ. Physiol. 283 (2): H750–9. doi:10.1152/ajpheart.00029.2002. PMID 12124224.
Further reading
- de la Monte SM, Lu BX, Sohn YK, et al. (2000). "Aberrant expression of nitric oxide synthase III in Alzheimer's disease: relevance to cerebral vasculopathy and neurodegeneration.". Neurobiol. Aging 21 (2): 309–19. doi:10.1016/S0197-4580(99)00108-6. PMID 10867216.
- Shaul PW (2002). "Regulation of endothelial nitric oxide synthase: location, location, location.". Annu. Rev. Physiol. 64: 749–74. doi:10.1146/annurev.physiol.64.081501.155952. PMID 11826287.
- Wu KK (2002). "Regulation of endothelial nitric oxide synthase activity and gene expression.". Ann. N. Y. Acad. Sci. 962: 122–30. doi:10.1111/j.1749-6632.2002.tb04062.x. PMID 12076969.
- Alp NJ, Channon KM (2005). "Regulation of endothelial nitric oxide synthase by tetrahydrobiopterin in vascular disease.". Arterioscler. Thromb. Vasc. Biol. 24 (3): 413–20. doi:10.1161/01.ATV.0000110785.96039.f6. PMID 14656731.
- Tai SC, Robb GB, Marsden PA (2005). "Endothelial nitric oxide synthase: a new paradigm for gene regulation in the injured blood vessel.". Arterioscler. Thromb. Vasc. Biol. 24 (3): 405–12. doi:10.1161/01.ATV.0000109171.50229.33. PMID 14656742.
- Kawashima S, Yokoyama M (2004). "Dysfunction of endothelial nitric oxide synthase and atherosclerosis.". Arterioscler. Thromb. Vasc. Biol. 24 (6): 998–1005. doi:10.1161/01.ATV.0000125114.88079.96. PMID 15001455.
- Duda DG, Fukumura D, Jain RK (2004). "Role of eNOS in neovascularization: NO for endothelial progenitor cells.". Trends in molecular medicine 10 (4): 143–5. doi:10.1016/j.molmed.2004.02.001. PMID 15162796.
PDB gallery 1d0c: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 3-BROMO-7-NITROINDAZOLE (H4B FREE)1d0o: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 3-BROMO-7-NITROINDAZOLE (H4B PRESENT)1d1v: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH S-ETHYL-N-PHENYL-ISOTHIOUREA (H4B BOUND)1d1w: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 2-AMINOTHIAZOLINE (H4B BOUND)1d1x: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 1,4-PBITU (H4B BOUND)1d1y: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 1,3-PBITU (H4B FREE)1dm6: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH N-(4-CHLOROPHENYL)-N'-HYDROXYGUANIDINE (H4B FREE)1dm7: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH HOMOARGININE (H4B FREE)1dm8: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 1,2,4-TRIAZOLE-CARBOXAMIDINE (H4B BOUND)1dmi: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 6S-H4B1dmj: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 5,6-CYCLIC-TETRAHYDROPTERIDINE1dmk: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 4-AMINO-6-PHENYL-TETRAHYDROPTERIDINE1ed4: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH IPITU (H4B FREE)1ed5: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH NNA(H4B FREE)1ed6: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH L-NIO (H4B FREE)1foi: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 1400W(H4B-FREE)1foj: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH 7-NITROINDAZOLE-2-CARBOXAMIDINE (H4B PRESENT)1fol: REDUCED BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH L-ARG(H4B-FREE)1foo: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH L-ARG AND NO(H4B-FREE)1fop: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH L-ARG AND NO(H4B-BOUND)1i83: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE HEME DOMAIN COMPLEXED WITH N1,N14-BIS((S-METHYL)ISOTHIOUREIDO)TETRADECANE (H4B FREE)1m9j: human endothelial nitric oxide synthase with chlorzoxazone bound1m9k: Human Endothelial Nitric Oxide Synthase with 7-Nitroindazole Bound1m9m: human endothelial nitric oxide synthase with 6-nitroindazole bound1m9q: human endothelial nitric oxide synthase with 5-nitroindazole bound1m9r: human endothelial nitric oxide synthase with 3-Bromo-7-Nitroindazole bound1nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE1p6l: Bovine endothelial NOS heme domain with L-N(omega)-nitroarginine-2,4-L-diaminobutyric amide bound1p6m: Bovine endothelial NOS heme domain with (4S)-N-(4-amino-5-[aminoethyl]aminopentyl)-N'-nitroguanidine bound1p6n: Bovine endothelial NOS heme domain with L-N(omega)-nitroarginine-(4R)-amino-L-proline amide bound1q2o: Bovine endothelial nitric oxide synthase N368D mutant heme domain dimer with L-N(omega)-nitroarginine-2,4-L-diaminobutyramide bound1rs8: Bovine endothelial NOS heme domain with D-lysine-D-nitroarginine amide bound1rs9: Bovine endothelial NOS heme domain with D-phenylalanine-D-nitroarginine amide bound1zzs: Bovine eNOS N368D single mutant with L-N(omega)-Nitroarginine-(4R)-Amino-L-Proline Amide Bound1zzt: Bovine eNOS N368D/V106M double mutant with L-N(omega)-Nitroarginine-(4R)-Amino-L-Proline Amide Bound2g6o: Structure of bovine eNOS heme domain (BH4-free) complexed with CO2hx2: Bovine eNOS heme domain complexed with (4S)-N-{4-Amino-5-[(2-aminoethyl)-hydroxyamino]-pentyl}-N'-nitroguanidine2nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE SUBSTRATE COMPLEX3nos: HUMAN ENDOTHELIAL NITRIC OXIDE SYNTHASE WITH ARGININE SUBSTRATE3nse: BOVINE ENOS, H4B-FREE, SEITU COMPLEX4nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, H4B-FREE, L-ARG COMPLEX5nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, H4B-FREE, HYDROXY-ARG COMPLEX6nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, H4B-FREE, CANAVANINE COMPLEX7nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, H4B-FREE, ADMA COMPLEX8nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, NNA COMPLEX9nse: BOVINE ENDOTHELIAL NITRIC OXIDE SYNTHASE, ETHYL-ISOSELENOUREA COMPLEXOxidoreductases: dioxygenases, including steroid hydroxylases (EC 1.14) 1.14.11: 2-oxoglutarate 1.14.13: NADH or NADPH Flavin-containing monooxygenase (FMO1, FMO2, FMO3, FMO4, FMO5) - Nitric oxide synthase (NOS1, NOS2, NOS3) - Cholesterol 7 alpha-hydroxylase - Methane monooxygenase - 3A4 - Lanosterol 14 alpha-demethylase1.14.14: reduced flavin or flavoprotein 1.14.15: reduced iron-sulfur protein 1.14.16: reduced pteridine (BH4 dependent) 1.14.17: reduced ascorbate 1.14.18-19: other 1.14.99 - miscellaneous B enzm: 1.1/2/3/4/5/6/7/8/10/11/13/14/15-18, 2.1/2/3/4/5/6/7/8, 2.7.10, 2.7.11-12, 3.1/2/3/4/5/6/7, 3.1.3.48, 3.4.21/22/23/24, 4.1/2/3/4/5/6, 5.1/2/3/4/99, 6.1-3/4/5-6 monoamine glutamate→GABAanabolism: Glutamate decarboxylase
catabolism: 4-aminobutyrate aminotransferase · 4-aminobutyrate transaminasearginine→NO choline→Acetylcholine anabolism: Choline acetyltransferase
catabolism: Cholinesterase (Acetylcholinesterase, Butyrylcholinesterase)Categories:- Human proteins
- Chromosome 7 gene stubs
- EC 1.14.13
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